Over the past few years an experimentally consistent model of chromatin structure has emerged that postulates the presence of regularly repeating subunits joined by short segments of DNA. These studies have provided a conceptual framework for the elucidation of the structure about transcriptionally active genes in chromatin. We have chosen the globin and ovalbumin genes as model systems for the elucidation of the structure of specific genes in chromatin and the mechanism through which this information is expressed. Coordinately, we are examining the integrated, C-type oncornavirus genome with the goal of further understanding the control of gene expression in higher organisms and, ultimately, the mechanism of transformation of the oncogenic viruses. One approach we have chosen involves dissection of the eucaryotic chromosome with a variety of deoxyribonucleases. Analysis of the products generated has permitted us to demonstrate that while histones reside on transcriptionally active segments of the genome, these regions are in an active conformation clearly distinguishable from the bulk of transcriptionally inert genomic DNA. Future studies are proposed which are designed to elucidate those factors responsible for the induction and maintenance of an active conformation about the transcribing segments of the genome. In concert with these studies, we have devised a means for gene isolation utilizing transfection of DNA fragments as a bioassay. These studies should permit us to examine the structure and expression of this gene both in vitro and when integrated into the chromosome of recipient cells.